Transition-Metal-Catalyzed Highly Selective Tandem Cyclization Of Enyne Compounds

Heterocyclic structures are present in most natural and synthetic molecules with important biological activity. Therefore, the discovery of novel efficient cyclization/cycloaddition reactions is important to access natural products and to explore a broad range of complex scaffolds with potentially enhanced bioactivity. Transition-metal-catalyzed domino reactions are unrivaled in their ability to provide rapid access to architecturally complex molecules from relatively simple acyclic starting materials.We have developed efficient routes to heterocyclic or polycyclic fused compounds, which may have potential biological activity and other valuable applications, from two kinds of eneyne compounds under the catalysis of transition-metal catalysts through the intra and intermolecular cyclizations.The first kind of substrates we employed are electron-deficient eneyne compounds, which were named as ketone compounds. We achieved four different types of cycloaddition reactions from conjugated eneyne ketone compounds under the catalysis of gold, silver and rhodium catalysts. Gold or silver-catalyzed cyclization of conjugated eneyne ketone compounds 1 afforded a furanyl gold or silver carbocation intermediate A. This intermediate would react withα,β-unsaturated imines to afford fused heterobicyclic furo[3,4-c] azepines by unusual [4+3] cycloaddition and 1,2-alkyl migration. Highly diastereoselective [3+2] cycloaddition of intermediate A with 3-styryl-1H-indole would produce highly substituted cyclopenta[c]furans. Gold(I) or silver(I) catalyzed usual [4+3] cyclization of intermediate A with 1,3-diphenylisobenzofuran provided a diastereoselective access to highly fused polycyclic compounds. It is noteworthy that the phosphine ligands of the metal catalyst played an important role in switching the diastereoselectivity. Furthermore, Rhodium-catalyzed cyclization of conjugated eneyne ketone compounds 1 afforded a furanyl cyclorhodium intermediate B'. This intermediate would react with alkynes to afford functional cyclopenta[c]furans by [3+2] cycloaddition under the atmosphere of carbon oxide.The second kind of substrates we employed are ortho-alkynylaryl aldehyde oximes and their derivatives. Isoquinoline N-oxide could be efficiently afforded by gold(I)-catalyzed intramolecular cyclization reaction of ortho-alkynylaryl aldehyde oximes. In addition, indoisoquinoline N-oxide could also be produced by 12-mediated electrophilic cyclization of ortho-alkynylaryl aldehyde oximes. The substituted group R of the oximes control the pattern of the cyclization, when R is allyl or alkyl group, the AgOTf catalyzed reaction affords isoquinoline, isoquinolin-(2H)-ones were produced when R is an acetyl group, respectively.